Dead space ventilation promotes alveolar hypocapnia reducing surfactant secretion by altering mitochondrial function
| Autor: | Leonie Schulte-Uentrop, Marc-Oliver Tritt, Kai Heckel, Sonja Schrepfer, Martina Kiefmann, Alwin E. Goetz, Rainer Kiefmann, Paula Keller, Cynthia Olotu, Sascha Tank |
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| Rok vydání: | 2018 |
| Předmět: |
Pulmonary and Respiratory Medicine
ARDS medicine.medical_specialty Atelectasis Pulmonary compliance 03 medical and health sciences 0302 clinical medicine Pulmonary surfactant Hypocapnia Internal medicine medicine Tidal Volume Animals 030304 developmental biology 0303 health sciences Respiratory Distress Syndrome Lung medicine.diagnostic_test business.industry Pulmonary Surfactants medicine.disease Mitochondria Rats Pulmonary Alveoli Disease Models Animal medicine.anatomical_structure Bronchoalveolar lavage Endocrinology 030220 oncology & carcinogenesis Breathing business |
| Zdroj: | Thorax. 74(3) |
| ISSN: | 1468-3296 |
| Popis: | BackgroundIn acute respiratory distress syndrome (ARDS), pulmonary perfusion failure increases physiologic dead space ventilation (VD/VT), leading to a decline of the alveolar CO2 concentration [CO2]iA. Although it has been shown that alveolar hypocapnia contributes to formation of atelectasis and surfactant depletion, a typical complication in ARDS, the underlying mechanism has not been elucidated so far.MethodsIn isolated perfused rat lungs, cytosolic or mitochondrial Ca2+ concentrations ([Ca2+]cyt or [Ca2+]mito, respectively) of alveolar epithelial cells (AECs), surfactant secretion and the projected area of alveoli were quantified by real-time fluorescence or bright-field imaging (n=3–7 per group). In ventilated White New Zealand rabbits, the left pulmonary artery was ligated and the size of subpleural alveoli was measured by intravital microscopy (n=4 per group). Surfactant secretion was determined in the bronchoalveolar lavage (BAL) by western blot.ResultsLow [CO2]iA decreased [Ca2+]cyt and increased [Ca2+]mito in AECs, leading to reduction of Ca2+-dependent surfactant secretion, and alveolar ventilation in situ. Mitochondrial inhibition by ruthenium red or rotenone blocked these responses indicating that mitochondria are key players in CO2 sensing. Furthermore, ligature of the pulmonary artery of rabbits decreased alveolar ventilation, surfactant secretion and lung compliance in vivo. Addition of 5% CO2 to the inspiratory gas inhibited these responses.ConclusionsAccordingly, we provide evidence that alveolar hypocapnia leads to a Ca2+ shift from the cytosol into mitochondria. The subsequent decline of [Ca2+]cyt reduces surfactant secretion and thus regional ventilation in lung regions with high VD/VT. Additionally, the regional hypoventilation provoked by perfusion failure can be inhibited by inspiratory CO2 application. |
| Databáze: | OpenAIRE |
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